Colardo Mayra, Martella Noemi, Varone Michela, Pensabene Daniele, Caretti Giuseppina, Bianchini Gianluca, Aramini Andrea, Segatto Marco
Department of Biosciences and Territory, University of Molise, Pesche, Italy.
Department of Biosciences, University of Milan, Milan, Italy.
Acta Physiol (Oxf). 2025 Jul;241(7):e70067. doi: 10.1111/apha.70067.
Cancer cachexia is a severe metabolic disorder leading to skeletal muscle atrophy. Muscle wasting is a major clinical problem in cachectic patients, as it limits the efficacy of chemotherapeutic treatments and worsens quality of life. Nutritional support based on branched-chain amino acids (BCAA) has been shown to be a promising approach to counteract cachexia-induced muscle atrophy, but its efficacy is still debated. Furthermore, the putative role of di-alanine (Di-Ala) supplementation has yet to be evaluated. The present study therefore sought to assess whether BCAA supplementation, alone or in combination with a Di-Ala peptide, could attenuate muscle wasting in a preclinical model of cancer cachexia.
To this end, C26 tumor-bearing mice were administered BCAA supplementation, with or without Di-Ala. Body and muscle weights, as well as molecular, biochemical, and morphological analysis, were carried out to characterize prospective changes of markers involved in cachexia and muscle atrophy.
The main findings revealed that BCAA supplementation effectively prevented body weight loss and muscle atrophy. Of note, Di-Ala significantly amplified the effects of BCAA. These phenomena were found to be mediated by the suppression of pathways involved in protein catabolism.
Collectively, these results highlight that innovative formulations containing Di-Ala, capable of increasing BCAA bioavailability, may be efficacious in counteracting muscle atrophy, especially during mild-to-moderate cancer cachexia.
癌症恶病质是一种导致骨骼肌萎缩的严重代谢紊乱。肌肉萎缩是恶病质患者的一个主要临床问题，因为它限制了化疗的疗效并恶化了生活质量。基于支链氨基酸（BCAA）的营养支持已被证明是对抗恶病质引起的肌肉萎缩的一种有前景的方法，但其疗效仍存在争议。此外，补充二丙氨酸（Di-Ala）的假定作用尚未得到评估。因此，本研究旨在评估单独补充BCAA或与Di-Ala肽联合补充是否能减轻癌症恶病质临床前模型中的肌肉萎缩。
为此，对携带C26肿瘤的小鼠给予BCAA补充剂，添加或不添加Di-Ala。进行体重和肌肉重量以及分子、生化和形态学分析，以表征恶病质和肌肉萎缩相关标志物的预期变化。
主要研究结果表明，补充BCAA可有效防止体重减轻和肌肉萎缩。值得注意的是，Di-Ala显著增强了BCAA的作用。发现这些现象是由蛋白质分解代谢相关途径的抑制介导的。
总的来说，这些结果表明，含有Di-Ala的创新制剂能够提高BCAA的生物利用度，可能对对抗肌肉萎缩有效，尤其是在轻至中度癌症恶病质期间。
